In Vitro Inhibitory Effects of 8-O-Demethylmaritidine and Undulatine on Acetylcholinesterase and Their Predicted Penetration across the Blood-Brain Barrier

J Nat Prod. 2015 Jun 26;78(6):1189-92. doi: 10.1021/acs.jnatprod.5b00191. Epub 2015 Jun 1.

Abstract

Alzheimer's disease is the most common cause of dementia. Currently, acetylcholinesterase (AChE) inhibition is the most widely used therapeutic treatment. A large number of naturally occurring compounds have been found to inhibit AChE. In this report the mechanism of AChE inhibition of two Amaryllidaceae alkaloids, 8-O-demethylmaritidine (1) and undulatine (2), and their possible penetration across the blood-brain barrier have been studied. Both compounds act via a mixed inhibition mechanism. Based on the parallel artificial permeation assay (PAMPA) for the prediction of blood-brain barrier (BBB) penetration, only 2 should be able to cross the BBB by passive permeation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Alzheimer Disease / drug therapy
  • Amaryllidaceae Alkaloids / pharmacology*
  • Biological Transport / drug effects
  • Blood-Brain Barrier / drug effects*
  • Cholinesterase Inhibitors / pharmacology*
  • Humans
  • In Vitro Techniques
  • Molecular Structure

Substances

  • 8-demethylmaritidine
  • Amaryllidaceae Alkaloids
  • Cholinesterase Inhibitors
  • undulatine
  • Acetylcholinesterase